RESUMO
OBJECTIVES: To evaluate long-term results of adrenalectomy for primary aldosteronism (PA) and to identify prognostic factors associated. METHODS: Exhaustive retrospective review of all consecutive patients undergoing adrenalectomy for PA between 2002 and 2013 in our department. All patients underwent preoperative: clinical evaluation (age, sex, height, weight, systolic and diastolic BP under treatment, identification of anti-hypertension treatment), biological evaluation (potassium, renin, aldosterone) and radiological evaluation (CT and/or MRI). Blood pressure was assessed postoperatively at 1 month, 1 year, then at the date of the latest news. The patients were classified into three categories: cured (no antihypertensive therapy in postoperative associated with strictly lower blood pressures of 140/90mmHg), improved (decreased number of drugs or number unchanged but with better blood pressure control), and refractory (no change in the number of drug and blood pressure, or deterioration of one or other of these two parameters). RESULTS: We evaluated 43 patients, 23 men and 20 women, with a median follow-up of 74.4 months [16.8 to 141]. Pathological analysis described 34 adenomas (79%), 7 hyperplasias (16%) (5 micro-nodular and 2 macro-nodular) and 2 adrenocortical carcinoma (5%). The postoperative long-term assessment found 20% of cured patients (n=8), 65% of improved (n=26) and 15% of refractory (n=6). Prognostic factors associated with favorable long-term blood pressure outcome were those typically associated with ARS score [preoperative number of anti-hypertension drugs (P=0.005), BMI<25kg/m2 (P=0.009), and duration of hypertension (P=0.007)]. CONCLUSION: Adrenalectomy for PA is a long-term effective treatment for blood pressure control. Prognostic factors associated with long-term success are those conventionally described in ARS score. LEVEL OF EVIDENCE: 4.
Assuntos
Adrenalectomia , Hiperaldosteronismo/complicações , Hiperaldosteronismo/cirurgia , Hipertensão/etiologia , Hipertensão/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Bone mineral density (BMD) loss is poorly defined in lymphoma patients. The aim of this study was to measure the extent of BMD loss in newly diagnosed lymphoma patients receiving chemotherapy. PATIENTS AND METHODS: This was a prospective, single-center study conducted in patients aged≥18 years with previously confirmed lymphoma treated by chemotherapy. Patients with low baseline BMD defined as Z/T-score less than or equal to -2.5 and/or history of osteoporotic fractures were excluded. BMD was measured at baseline before initiating chemotherapy and 1 year later. Predictive factors of BMD loss were investigated. RESULTS: Forty-one lymphoma patients (31 males and 10 females) receiving chemotherapy were enrolled. The median age at diagnosis was 59 (range: 19-86) years. Histological subtypes were predominantly diffuse large B-cell lymphoma (58%), mostly stage III-IV (54%). All patients received chemotherapy and 22% of patients received second-line treatment due to relapse or progressive disease. Thirty-two patients were evaluable at 1 year. The mean BMD changes were: -2.7%±3.9% for lumbar spine (P<0.001), -2.2%±7.6% for femoral neck (P<0.01) and -2.6%±4.5% for total hip (P<0.0001). In multivariate analysis, predictive factors of BMD loss at baseline were (i) at lumbar spine: female gender (P=0.01), higher lactate dehydrogenase level (P=0.04) and lower creatinine clearance (P=0.01); (ii) at total hip: lower albumin (P=0.01), higher corrected serum calcium (P<0.01), lower alkaline phosphatase (AP) (P<0.01) and autologous stem cell transplant (P=0.03); and (iii) at femoral neck: higher corrected serum calcium (P=0.02) and lower bone AP (P=0.01). CONCLUSION: Adult patients with known lymphoma receiving chemotherapy experienced significant BMD loss at 1 year.
Assuntos
Antineoplásicos/uso terapêutico , Reabsorção Óssea/sangue , Linfoma/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Densidade Óssea , Reabsorção Óssea/patologia , Feminino , Colo do Fêmur/patologia , Humanos , Vértebras Lombares/patologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Adulto JovemRESUMO
Illegitimate G-protein coupled receptors are known to control cortisol secretion in adrenal adenomas and bilateral macronodular adrenal hyperplasias (BMAHs) causing Cushing's syndrome. In the present study, we have evaluated the role of glucagon in the regulation of cortisol secretion in 13 patients with BMAH or adrenocortical adenoma causing subclinical or overt Cushing's syndrome. Injection of glucagon provoked an increase in plasma cortisol in 2 patients. After surgery, immunohistochemical studies showed the presence of glucagon receptor-like immunoreactivity in clusters of spongiocytic cells in adrenal tissues from patients who were sensitive in vivo to glucagon. We also observed an in vitro cortisol response to vasoactive intestinal peptide from an adenoma, which was insensitive to glucagon and pituitary adenylate cyclase-activating peptide. Altogether, our data show that ectopic glucagon receptors are expressed in some adrenal cortisol-producing benign lesions. Our results also indicate that circulating glucagon may influence cortisol release under fasting conditions.
Assuntos
Glândulas Suprarrenais/patologia , Síndrome de Cushing/patologia , Glucagon/farmacologia , Peptídeos/farmacologia , Glândulas Suprarrenais/efeitos dos fármacos , Adenoma Adrenocortical/sangue , Adulto , Idoso , Síndrome de Cushing/sangue , Feminino , Humanos , Hidrocortisona/sangue , Hidrocortisona/metabolismo , Hiperplasia , Imuno-Histoquímica , Cinética , Masculino , Pessoa de Meia-Idade , Receptores de Glucagon/metabolismo , Adulto JovemRESUMO
Type 1 diabetes results from an interaction between genetic and environmental factors. Coxsackieviruses B (CV-B) are major environmental candidates, as suggested by epidemiological and experimental studies. The mechanisms leading to the disease involve interactions between the virus, host target tissue (pancreas) and the immune system. The infection of target cells with viruses can be prevented by antibodies. Conversely, the infection can be enhanced by antibodies. The antibody-dependent enhancement (ADE) of infection has been described with various viruses, especially Picornaviruses. In mice infected with CV-B3 this phenomenon resulted in an extended inflammatory reaction and myocarditis. In the human system non-neutralizing antibodies can increase the infection of monocytes with CV-B4 and stimulate the production of interferon (IFN)-α by these cells in vitro. CV-B4/immunoglobulin (Ig)G immune complexes interacted with a specific viral receptor [Coxsackievirus and adenovirus receptor (CAR)] and with IgG Fc fraction receptors (FcγRII and FcγRIII) at the surface of monocytes. The virus-antibody complexes are internalized (CAR) and receptors for the Fc of IgG (FcγRII and FcγRIII). Such antibodies have been detected in patients with type 1 diabetes and they could be responsible for the presence of enteroviral RNA and IFN-α in peripheral blood mononuclear cells (PBMC) of these individuals. The target of enhancing antibodies has been identified as the VP4 protein, which allowed the detection of these antibodies by enzyme-linked immunosorbent assay (ELISA). It cannot be excluded that antibodies enhancing the infection with CV-B may play a role in the pathogenesis of type 1 diabetes, induced or aggravated by these viruses. They can cause a viral escape from the immune response and may participate in the spreading of viruses to ß cells. Whether enhancing antibodies raised against VP4 can play a role in iterative homologous and/or heterologous CV-B infections and in the persistence of viruses within the host deserves further study.
Assuntos
Anticorpos Antivirais/imunologia , Anticorpos Facilitadores , Infecções por Coxsackievirus/imunologia , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/virologia , Enterovirus Humano B/imunologia , Animais , Anticorpos Antivirais/sangue , Infecções por Coxsackievirus/virologia , Humanos , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Células Secretoras de Insulina/imunologia , Células Secretoras de Insulina/virologia , Interferon gama/biossíntese , Camundongos , RNA Viral/sangueRESUMO
Throughout the world, millions of people suffer from fragilizing osteopathies such as osteomalacia and osteoporosis. Osteomalacia is a rare disorder, corresponding to mineralization abnormalities in adult bone, as opposed to rickets in children. Renal phosphate loss and hypophosphatasia are the main causes of vitamin-resistant osteomalacia. Diagnosis is based on clinical history, phosphocalcic metabolism assessment and, if necessary, molecular characterization, and must be rapid in order to initiate the most appropriate treatment and consider new treatments such as burosumab if necessary. Osteoporosis is characterized by reduced bone mass and strength, which increases the risk of fragility fracture. Fracture-related burden is expected to increase over the coming decades linked to the aging of population and a treatment gap. In order to reduce this treatment gap, it is important to develop two strategies: improvement of screening and of treatment. Systematic screening using the FRAX® fracture risk assessment tool could be useful to increase anti-osteoporosis medical treatment and reduce fracture rates. The question of treatment sequencing in osteoporosis is another challenge, notably after denosumab cessation, complicated by a decrease in bone mineral density and increased risk of fracture. New treatments are also available, including romosozumab, a humanized monoclonal antibody, which promotes bone formation and inhibits bone resorption by inhibiting sclerostin. Romosozumab is approved in several countries, including France, for treating severe osteoporosis in postmenopausal women at high risk of fracture and free of cardiovascular comorbidity. Endocrinologists need to be aware of these fragilizing osteopathies in order to improve both diagnosis and treatment.
Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Calcificação Fisiológica/efeitos dos fármacos , Osteomalacia/tratamento farmacológico , Osteoporose/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Osso e Ossos/efeitos dos fármacos , Feminino , Fraturas Ósseas/tratamento farmacológico , França , HumanosRESUMO
Viral RNA (vRNA) is found in mice inoculated with coxsackievirus-B4E2 (CV-B4E2). The CV-B4E2 infection of murine spleen cells in vitro is enhanced with CV-B4E2-infected mouse serum. It has been investigated whether monocyte/macrophages were targets of CV-B4E2 in mice. vRNA has been detected in spleen and bone marrow of infected animals. The levels of vRNA were higher in CD14+ cells than in CD14- spleen cells and in F4/80- cells than in F4/80+â¯spleen cells. Meanwhile, CD14+ cells and F4/80- cells were more permissive to CV-B4E2 in vitro and the infection was enhanced when the virus was mixed with immune serum. While CV-B4E2 infected BMDM cultures (98% F4/80+); however, the immune serum did not enhance the infection. In conclusion, CV-B4E2 infects monocytes (CD14+, F4/80-) and macrophages (CD14+, F4/80+) in vivo and immune serum can enhance the in vitro infection of these cells arising out of the spleen.
Assuntos
Infecções por Coxsackievirus/virologia , Enterovirus Humano B/crescimento & desenvolvimento , Macrófagos/virologia , Monócitos/virologia , Animais , Anticorpos Facilitadores , Medula Óssea/virologia , Modelos Animais de Doenças , Camundongos , RNA Viral/análise , Baço/virologiaRESUMO
OBJECTIVE: The use of an intravenous catheter with a rest period has been recommended to avoid false-positive results for hyperprolactinaemia and false-negative results for hypocortisolaemia. We tested the relevance of this recommendation. DESIGN: Plasma cortisol and prolactin levels were determined before (T-15) and after a 15-min rest period (T0) in 119 patients, 38 males (M) and 81 females (F). 52 of the 119 patients were known (K; 30 females and 22 males) and 67 unknown (UK; 49 females and 18 males) to the unit. RESULTS: Prolactin was lower after rest in women (12.3+/-22.7 ng/l vs 11.7+/-22.5 ng/ml, P=0.03), but not in men (6.2+/-4.5 ng/ml at T-15 vs 5.8+/-3.2 ng/ml at T0, P=0.09), in the UK subgroup (10.6+/-20.7 ng/ml at T-15 vs 10.1+/-20.9 ng/ml at T0, P=0.06) and in the K subgroup (10.1+/-16.7 ng/ml at T-15 vs 9.7+/-15.8 ng/ml at T0, P=0.08). None of the patients with prolactin levels higher than 20 ng/ml at T-15 diminished its prolactin value below this cut-off value. Plasma cortisol levels were lower after rest in women (17.9+/-5.9 microg/dl at T-15 vs 16.5+/-6.1 microg/dl at T0, P<0.0001), in the UK subgroup (18+/-6.1 microg/dl at T-15 vs 16.6+/-6.4 microg/dl at T0, P=0.0003) but not in men (18+/-4.4 microg/dl at T-15 vs 17.5+/-5.8 microg/dl at T0, P=0.47) and in the K subgroup (17.8+/-4.6 microg/dl at T-15 vs 17+/-5.4 microg/dl at T0, P=0.13). At T0, 3.3% and 15% of patients presented values below the cut-off value of 10 microg/dl (276 nmol/l) and 17 microg/dl (470 nmol/l), respectively. CONCLUSION: These results don't justify intravenous catheterisation with a rest period for plasma prolactin determination in contrast with plasma cortisol determination.
Assuntos
Coleta de Amostras Sanguíneas/métodos , Cateterismo Venoso Central/métodos , Hidrocortisona/sangue , Prolactina/sangue , Doenças das Glândulas Suprarrenais/sangue , Doenças das Glândulas Suprarrenais/diagnóstico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças da Hipófise/sangue , Doenças da Hipófise/diagnóstico , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/diagnóstico , Reprodutibilidade dos Testes , Fatores de TempoRESUMO
Parathormone (PTH), produced by parathyroid glands, is the main regulator of calcium homeostasis. Hypoparathyroidism (hypoPT), due to decrease of PTH production, is a rare disease. Symptoms are multiple, altering function of several organs and leading to a decrease of quality of life. Acquired etiologies, including thyroïdectomy, the main cause of hypoPT, can be distinguished from congenital etiologies, including genetic defects. HypoPT, which is classically treated by supplementation by calcium and active vitamin D, can now be treated by recombinant injection in certain indications as a poor control under classical therapy. Here are summarized current knowledge on etiologies, epidemiology, clinical manifestations and management of hypoPT.
Assuntos
Hipoparatireoidismo , Cálcio/metabolismo , Diagnóstico Diferencial , Técnicas de Diagnóstico Endócrino , Endocrinologistas/tendências , Doenças Genéticas Inatas/diagnóstico , Doenças Genéticas Inatas/epidemiologia , Doenças Genéticas Inatas/terapia , Humanos , Hipoparatireoidismo/diagnóstico , Hipoparatireoidismo/epidemiologia , Hipoparatireoidismo/etiologia , Hipoparatireoidismo/terapia , Padrões de Prática Médica/tendências , Receptores de Detecção de Cálcio/genética , Receptores de Detecção de Cálcio/metabolismoRESUMO
Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant hereditary syndrome (OMIM 131100) due to MEN1 gene mutations, predisposing to the development of hyperplasic and tumoral lesions of neuroendocrine tissues. Since the identification of the gene in 1997, more than 400 different mutations of MEN1 have been registered. Genotypic analysis of MEN1 remains fastidious and must be reserved to targeted situations. If the lesions appear in a familial assessed context, there is a strong argument to search for MEN1 mutation. This is not the case in a sporadic context. With experience acquired in our laboratory, we evaluated the frequency of MEN1 mutations in patients with sporadic presentations. Our aim was to better define criteria for MEN1 genotypic analysis. One hundred and twenty four blood samples from unrelated patients, who gave their written informed consent, were analyzed. These patients exhibited 1 to 4 manifestations of MEN1 without any familial context. After DNA extraction, the analysis was undertaken by PCR-sequencing of all the MEN1 coding exons and exon/intron boundaries or by PCR of the pre-screened fragments alone, a technique made possible by indirect screening mutation methods. Mutations were identified by comparing the sequences to the reference MEN1 sequence available from GENBANK (U93237.1). Mutations were identified in 19 patients, with variable prevalence according to clinical manifestations: 100% for patients with 4 manifestations, 45.5% for patients with 3 manifestations, 19% for patients with 2 manifestations and 2% for patients with only one manifestation. Mutations were: 11 point variations (58%), including 2 splicing sites and 8 frameshift mutations (42%) including 5 deletions, 2 insertions and 1 insertion/deletion; one mutation was identified twice. We showed a relationship between clinical presentation and MEN1 mutation identification, especially with the number of clinical manifestations but also with the type of manifestation. Pancreatic manifestations were significantly linked with probability of mutation. In a sporadic context with at least two established manifestations of MEN1, the overall probability of identifying a mutation was 26%, warranting MEN1 genotypic analysis.
Assuntos
Cromossomos Humanos Par 11 , Testes Genéticos , Neoplasia Endócrina Múltipla Tipo 1/genética , Adulto , DNA/sangue , DNA/genética , DNA/isolamento & purificação , Diagnóstico Diferencial , Frequência do Gene , Humanos , Pessoa de Meia-Idade , Dados de Sequência Molecular , Neoplasia Endócrina Múltipla Tipo 1/classificação , Neoplasia Endócrina Múltipla Tipo 1/diagnóstico , MutaçãoRESUMO
Acromegaly is associated with increased morbidity and mortality. Cardiovascular complications are the major predictors of mortality. Age and duration of symptoms are the major determinants of acromegalic cardiopathy. Successful control of acromegaly reverse cardiovascular abnormalities. Herein, we review clinical, biological and histopathological findings in elderly people. Treatments and side effects in relation with aging are questioned.
Assuntos
Acromegalia , Envelhecimento , Acromegalia/complicações , Acromegalia/mortalidade , Acromegalia/patologia , Acromegalia/terapia , Idoso , Doenças Cardiovasculares/complicações , Humanos , Fatores de Risco , Fatores de TempoRESUMO
Endocrine complications (particularly gonadal, hypothalamic-pituitary and metabolic) of childhood cancer treatments are common in young adults. Gonadal damage may be the result of chemotherapy or radiotherapy. Fertility preservation must be systematically proposed before initiation of gonadotoxic treatment if only the child is eligible. Hypothalamic-pituitary deficiency is common after brain or total-body irradiation, the somatotropic axis is the most sensitive to irradiation. Pituitary deficiency screening must be repeated since this endocrine consequence can occur many years after treatment. Hormone replacement must be prudent particularly in case of treatment with growth hormone or steroids. Metabolic syndrome, diabetes and cardiovascular damage resulting from cancer treatments contribute to the increase of morbidity and mortality in this population and should be screened routinely even if the patient is asymptomatic. The multidisciplinary management of these adults must be organized and the role of the endocrinologist is now well established.
Assuntos
Antineoplásicos/efeitos adversos , Doenças do Sistema Endócrino/etiologia , Neoplasias/terapia , Radioterapia/efeitos adversos , Criança , Feminino , Preservação da Fertilidade , Gônadas/efeitos dos fármacos , Gônadas/efeitos da radiação , Terapia de Reposição Hormonal , Humanos , Doenças Hipotalâmicas/etiologia , Masculino , Doenças Metabólicas/etiologia , Doenças da Hipófise/etiologia , Sobreviventes , Adulto JovemRESUMO
To date, only one study has demonstrated increased serum inhibin levels in women with polycystic ovary syndrome (PCOS). Moreover, no relationship between serum inhibin and either FSH or androgen levels has been noted. This lack of data could be due to 1) the heterogeneity of PCOS and the small sample size of previous studies, and/or 2) the complexity of circulating inhibin molecular forms, which hinders the precise evaluation of bioactive inhibin. In the present study, alpha-inhibin levels were assayed in the serum of 61 healthy women and 72 PCOS patients by means of an alpha-alpha enzyme-linked immunosorbent assay. Serum alpha-inhibin levels together with LH and androstenedione (A) levels were significantly increased in PCOS women (mean +/- SD, 1.45 +/- 0.55 vs. 0.94 +/- 0.36 U/mL in controls; P < 0.001). Moreover, simple and partial regression analysis demonstrated that serum A levels were positively and independently correlated to serum alpha-inhibin (r = 0.32; P < 0.01) and LH levels (r = 0.48; P < 0.001) in PCOS. The respective influences of alpha-inhibin and LH on A variability were 20% and 80%, as determined by multiple regression analysis. In conclusion, in agreement with recent in vitro data, our in vivo results argue for a role of inhibin in the hyperandrogenism of PCOS together with, but independently from, that of LH. Further studies are needed to determine whether this effect is produced by inhibin A and/or B.
Assuntos
Androstenodiona/sangue , Inibinas , Peptídeos/sangue , Síndrome do Ovário Policístico/sangue , Adolescente , Adulto , Androgênios/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Hormônio Luteinizante/sangue , Valores de Referência , Análise de RegressãoRESUMO
We report the case of a 44-year-old obese diabetic woman admitted for fever. Blood cultures grew Staphylococcus Aureus and antibiotherapy was started. Iliac abscess was diagnosed and surgical drainage done. Clinical evolution was marked by metastatic dissemination: sacroiliac osteolysis, right shoulder osteoarthritis, spondylitis of the third lumbar vertebra and pulmonary localizations. This case-report shows diagnosis and treatment difficulties of an iliac muscle abscess with metastatic localization in a diabetic patient.
Assuntos
Abscesso/diagnóstico , Complicações do Diabetes , Obesidade , Infecções Estafilocócicas/diagnóstico , Abscesso/complicações , Abscesso/microbiologia , Adulto , Antibacterianos , Diagnóstico Diferencial , Quimioterapia Combinada/uso terapêutico , Feminino , Humanos , Rifampina/uso terapêutico , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/tratamento farmacológico , Resultado do TratamentoRESUMO
UNLABELLED: Slow onset type 1 diabetes is an heterogeneous entity. Its clinical features may mimick type 2 diabetes but its pathophysiological mechanisms are close to type 1 diabetes. AIM OF THE STUDY: To find out the frequencies, levels and associations of ICA, GADab and IA-2ab in type 2 diabetic patients with atypical phenotype. To compare it to type 1 diabetes. PATIENTS AND METHODS: ICA, GADab and IA-2ab were determined in: - 61 patients (age at diagnosis 48.2 +/- 10, range 36-73 years) with an initial diagnosis of type 2 diabetes but having at least one symptom suggesting a slow type 1 diabetes (loss of weight, absence of obesity at diagnosis or secondary failure of oral hypoglycaemic agents). - 70 patients with type 1 diabetes (age 18 +/- 8.9, range 2-35 years). Clinical data evaluated in slow type 1 were maximal BMI, BMI and loss of weight at diagnosis and autoimmune disease. Fasting C-peptide and insulinemia were also assessed. RESULTS: (Slow type 1 diabetes versus type 1 diabetes). ICA (43% vs 70%; p <0.01) and IA-2ab (16% vs 75%; p <0.01) were more frequent in type 1. GADab were as frequent (62% vs 74%). Association of the three antibodies (15.7% vs 58.5%; p <0.05) were more frequent in type 1. Prevalence of GADab alone (27.5% vs 7.5%; p <0.05) was higher in slow type 1 diabetes and with higher levels (median 55.5 UI/ml vs 17 UI/ml; p <0.01). There was no difference for levels of ICA (25.5 UJDF/ml vs 28 UJDF/ml) or IA-2ab (11.5 UI/ml vs 38.5 UI/ml). BMI of GADab positive patients was lower. Delay of insulinotherapy was shorter in GADab or ICA positive patients. We did not find any relationship between antibodies presence and fasting C-peptide or insulinemia. CONCLUSION: Slow type 1 diabetes should be evoked in atypical type 2 diabetes. Slow onset type 1 diabetic patients have different autoimmune patterns suggesting a different pathophysiological process. GADab and ICA are useful markers to predict future insulinopenia.
Assuntos
Autoanticorpos/sangue , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 2/imunologia , Adulto , Idade de Início , Idoso , Biomarcadores/sangue , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Progressão da Doença , Feminino , Glutamato Descarboxilase/imunologia , Humanos , Ilhotas Pancreáticas/imunologia , Masculino , Pessoa de Meia-Idade , Redução de PesoRESUMO
AIM: These case reports demonstrate that, at the individual level, blood metformin concentrations and metformin effects on lactate do not always correlate. METHODS: We report here on two unusual cases: metformin accumulation in the absence of hyperlactataemia; and metformin-induced hyperlactataemia with no metformin accumulation. RESULTS: Patient #1 presented with severe kidney failure, severe acidosis (pH: 7.04), normal lactataemia (0.90 mmol/L) and marked metformin accumulation. Patient #2 presented with hyperlactataemia, even after dose reduction, during otherwise well-tolerated metformin treatment. Arterial lactate levels were 8.8, 8.2 and 4.7 mmol/L during metformin therapy with daily doses of 2550, 1700 and 850 mg, respectively. After withdrawal, metformin was reintroduced for 5-day periods at 500 mg/day up to 2000 mg/day with washout intervals. Lactate concentration, normal at baseline, rapidly exceeded 2 mmol/L after metformin administration. CONCLUSION: These clinical data suggest a new concept for metformin therapy: there may be either resistance or, conversely, hypersensitivity to metformin effects on lactate generation according to the individual patient.
Assuntos
Acidose Láctica/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hiperlactatemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Ácido Láctico/sangue , Metformina/efeitos adversos , Acidose Láctica/sangue , Idoso , Diabetes Mellitus Tipo 2/sangue , Esquema de Medicação , Hipersensibilidade a Drogas , Resistência a Medicamentos , Feminino , Humanos , Hiperlactatemia/sangue , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/metabolismo , Masculino , Metformina/administração & dosagem , Metformina/metabolismo , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Type 1 diabetes (T1D) is due to the loss of both beta-cell insulin secretion and glucose sensing, leading to glucose variability and a lack of predictability, a daily issue for patients. Guidelines for the treatment of T1D have become stricter as results from the Diabetes Control and Complications Trial (DCCT) demonstrated the close relationship between microangiopathy and HbA1c levels. In this regard, glucometers, ambulatory continuous glucose monitoring, and subcutaneous and intraperitoneal pumps have been major developments in the management of glucose imbalance. Besides this technological approach, islet transplantation (IT) has emerged as an acceptable safe procedure with results that continue to improve. Research in the last decade of the 20th century focused on the feasibility of islet isolation and transplantation and, since 2000, the success and reproducibility of the Edmonton protocol have been proven, and the mid-term (5-year) benefit-risk ratio evaluated. Currently, a 5-year 50% rate of insulin independence can be expected, with stabilization of microangiopathy and macroangiopathy, but the possible side-effects of immunosuppressants, limited availability of islets and still limited duration of insulin independence restrict the procedure to cases of brittle diabetes in patients who are not overweight or have no associated insulin resistance. However, various prognostic factors have been identified that may extend islet graft survival and reduce the number of islet injections required; these include graft quality, autoimmunity, immunosuppressant regimen and non-specific inflammatory reactions. Finally, alternative injection sites and unlimited sources of islets are likely to make IT a routine procedure in the future.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 1/cirurgia , Hemoglobinas Glicadas/metabolismo , Imunossupressores/uso terapêutico , Células Secretoras de Insulina/metabolismo , Transplante das Ilhotas Pancreáticas , Proteína C-Reativa/metabolismo , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/fisiopatologia , Feminino , Humanos , Células Secretoras de Insulina/imunologia , Transplante das Ilhotas Pancreáticas/efeitos adversos , Transplante das Ilhotas Pancreáticas/métodos , Masculino , Seleção de Pacientes , Guias de Prática Clínica como Assunto , Prognóstico , Qualidade de Vida , Reprodutibilidade dos Testes , Medição de Risco , Resultado do TratamentoRESUMO
Because of antidiuretic hormone (ADH) disorder on production or function we can observe dysnatremia. In the absence of production by posterior pituitary, central diabetes insipidus (DI) occurs with hypernatremia. There are hereditary autosomal dominant, autosomal recessive or X- linked forms. When ADH is secreted but there is an alteration on his receptor AVPR2, it is a nephrogenic diabetes insipidus in acquired or hereditary form. We can make difference on AVP levels and/or on desmopressine response which is negative in nephrogenic forms. Hyponatremia occurs when there is an excess of ADH production: it is a euvolemic hypoosmolar hyponatremia. The most frequent etiology is SIADH (syndrome of inappropriate secretion of ADH), a diagnostic of exclusion which is made after eliminating corticotropin deficiency and hypothyroidism. In case of brain injury the differential diagnosis of cerebral salt wasting (CSW) syndrome has to be discussed, because its treatment is perfusion of isotonic saline whereas in SIADH, the treatment consists in administration of hypertonic saline if hyponatremia is acute and/or severe. If not, fluid restriction demeclocycline or vaptans (antagonists of V2 receptors) can be used in some European countries. Four types of SIADH exist; 10 % of cases represent not SIADH but SIAD (syndrome of inappropriate antidiuresis) due to a constitutive activation of vasopressin receptor that produces water excess. c 2013 Published by Elsevier Masson SAS.
Assuntos
Hipernatremia/etiologia , Hiponatremia/etiologia , Vasopressinas/fisiologia , Diabetes Insípido/diagnóstico , Diabetes Insípido/genética , Diabetes Insípido/fisiopatologia , Diabetes Insípido Nefrogênico/diagnóstico , Diabetes Insípido Nefrogênico/genética , Diabetes Insípido Nefrogênico/fisiopatologia , Diagnóstico Diferencial , Humanos , Hipernatremia/terapia , Hiponatremia/terapia , Síndrome de Secreção Inadequada de HAD/complicações , Síndrome de Secreção Inadequada de HAD/diagnóstico , Doenças da Hipófise/complicações , Doenças da Hipófise/genética , Doenças da Hipófise/fisiopatologia , Neuro-Hipófise/metabolismo , Receptores de Vasopressinas/fisiologia , Cloreto de Sódio/administração & dosagem , Desequilíbrio Hidroeletrolítico/fisiopatologiaRESUMO
The increased prevalence of certain diseases, along with the development of new technologies and industrialization raised the possibility of the involvement of environmental factors, industrial products, nutritional factors, infections, drugs... and endocrine disruptors. These factors may interfere via signaling pathways specific to the organism. Endocrine Disrupting Chemicals (EDCs) have been redefined by the Endocrine Society in 2012 as "exogenous chemical, or mixture of chemicals, that can interfere with any aspect of hormone action". They have therefore potentially deleterious effects on development, growth, metabolism, reproduction, the nervous, immune and cardiovascular systems. Therefore, they constitute a real public health issue. Their long half-life may explain delayed effects and their often lipophilic character may promote maternofetal transmission. Except diethylstilbestrol (DES), few formal proofs have been made on the direct role of EDCs ; arguments are based on cross-sectional studies, in vitro models and animal models. Basic research puts insight into mechanisms of action of EDCs but many questions remain unanswered. Epidemiological data are difficult to interpret because of interindividual differences in susceptibility to EDCs and of nonlinear/nonmonotonique action (as opposed to toxic dose effect), multiple interactions between environmental agents (additive effects and/or synergistic and/or antagonists), the role of the window of exposure, latency, and the possibility of transgenerational effects.
Assuntos
Disruptores Endócrinos , Endocrinologia , Congressos como Assunto , Dietilestilbestrol , Disruptores Endócrinos/farmacologia , Disruptores Endócrinos/toxicidade , Sistema Endócrino/efeitos dos fármacos , Poluentes Ambientais/farmacologia , Poluentes Ambientais/toxicidade , Meia-Vida , Hormônios , Humanos , Resíduos IndustriaisRESUMO
OBJECTIVES: There are very few studies evaluating the efficacy of sleeve gastrectomy on the metabolic syndrome, truly a worldwide pandemic. The main objective of this study was to retrospectively determine the evolution of the metabolic syndrome and its associated comorbidities (type 2 diabetes, arterial hypertension, and dyslipidemia) at 24 months after sleeve gastrectomy. The secondary objective was to determine the predictive factors for resolution of this syndrome. MATERIAL AND METHODS: Between July 2004 and February 2008, 241 patients with morbid obesity (males: 17%) underwent sleeve gastrectomy in our center. Patients were seen in combined medical and surgical outpatient postoperative follow-up consultation at 3, 6, 12 and 24 months. Patients were classed as responders or not, according to whether or not the metabolic syndrome (as defined according to the National Cholesterol Education Program-Adult Treatment Panel III [NCEP-ATPIII]) disappeared at 24 months follow-up. RESULTS: Thirty-six patients (15% of all patients, 30% of males) presented initially with metabolic syndrome. Twenty-six patients (72%) still had metabolic syndrome at 6 months, 17 patients (47%) at 12 months, and 13 patients (36%) at 24 months. The main parameters that regressed after sleeve gastrectomy were type 2 diabetes and hypertriglyceridemia. In univariate analysis, only one parameter (systolic blood pressure) appeared to be a factor of non-resolution of the metabolic syndrome at 24 months. CONCLUSION: Our study showed that sleeve gastrectomy reduced the incidence of the metabolic syndrome and several of its components.